Pre-filled package containing unit dose of medical gas and method of making the same

ABSTRACT

A unit dose, gas-filled syringe is provided which is filled with gas and packaged in a gas barrier material prior to use to increase shelf-life, that is, to minimize gas leakage and dilution of the contents of the syringe. The syringe is filled with a selected gas and sealed inside a container made from a high gas barrier material. The container is also filled with the selected gas. The container material is selected to have a gas transmission rate sufficient to prevent the selected gas from diffusing out of the container into the atmosphere. The volume of gas in the container is greater that atmospheric pressure to prevent atmospheric contaminants from entering the container and syringe.

CROSS-REFERENCE TO RELATED APPLICATION

This application is a continuation of application Ser. No. 09/563,672,filed May 2, 2000, now issued as U.S. Pat. No. 6,494,314, which is acontinuation of application Ser. No. 09/252,682, filed Feb. 22, 1999,now issued as U.S. Pat. No. 6,073,759, which was a continuation-in-partof application Ser. No. 08/838,824, filed Apr. 10, 1997, now abandoned,each of which is hereby incorporated by reference in its entirety.

FIELD OF THE INVENTION

The invention relates generally to a pre-filled package containing aunit dose of medical gas and a method of making same. The invention isfurther directed to a method of introducing a unit dose for a gas into apatient using the prefilled syringe.

BACKGROUND OF THE INVENTION

Gas-filled syringes are useful for a number of applications such assurgical procedures involving the injection of a gas bubble into apatient's body. For example, a retinal tear can be treated using anintraocular surgical procedure during which a gas such as sulfurhexafluoride (SF₆) or perfluoropropane (C₃F₈) is injected into the eyefor gas tamponage. Carbon dioxide (CO₂) gas can be injected into a bloodvessel to facilitate percutaneous angioscopy. Nitric oxide (NO) gas andNO-releasing compounds can also be used to treat a number of medicalconditions. For example, NO and NO-releasing compounds can be used fortreatment of male impotence, inhibition of DNA synthesis andmitochondrial respiration in tumor cells, and relaxation of vascularsmooth muscle for control of hypertension.

Gases used for surgery are often expensive and not available forpurchase in ready-to-use form. Currently, gases for surgical proceduresare purchased in a pressurized tank. Syringes are filled directly fromthe tank using a filling line. When a syringe is disconnected from thefilling line, the gas in the filling line is released into theatmosphere. Thus, this method of preparing syringes for surgery isdisadvantageous because a significant amount of gas is wasted. Due tothe busy environment of a hospital, shut-off valves on gas tanks arefrequently left open accidentally, causing an even greater amount of gasto be wasted than when gas syringes are being filled.

In addition to the problem of wasting expensive gases, a more seriousclinical problem associated with filling syringes from gas tanks isdilution of the gas in the syringe prior to surgery. Syringes aresometimes prepared on the morning of the day they are to be used insurgery. The syringes are then placed in the operating room with othersurgical devices until they are needed, which can be several hourslater. Experiments have shown that leakage of gas from a syringe over arelatively short period of time can cause clinically significantdilution of the gas dose and therefore increase the risk of surgicalcomplications. For instance, the concentration of sulfur hexafluoride ina plastic syringe has been observed to decrease from 97% at 30 secondsafter aspiration to 76% at 60 minutes and 2% at 18 hours pastaspiration.

SUMMARY OF THE INVENTION

The present invention overcomes the above-described disadvantagesassociated with known methods for preparing gas-filled syringes, whilealso realizing a number of advantages. In accordance with one aspect ofthe invention, a unit dose, gas-filled syringe is provided which isfilled with gas and packaged in a gas barrier material prior to use toincrease shelf-life, that is, minimize gas leakage and dilution of thecontents of the syringe. The syringe is initially filled with a selectedgas and sealed inside a container made from a high gas barrier material.The container is then also filled with the selected gas. The containermaterial is selected to have a gas transmission rate sufficient toprevent the selected gas from diffusing out of the container into theatmosphere and to prevent atmospheric gas contaminants from entering thecontainer. The gas is a pharmaceutically acceptable gas for injectinginto the body of an animal. The gas is substantially free of oxygen andair and is at least 70% pure, and preferably 97% pure by volume.

In accordance with another aspect of the present invention, a method ofpackaging a gas-filled syringe is provided which comprises the steps offorming a container from a gas barrier material to enclose the syringe,placing the gas-filled syringe in the container, filling the containerwith the same gas as in the pre-filled gas syringe, and sealing thecontainer to retain the gas and the syringe therein.

In accordance with yet another aspect of the present invention, a methodof packaging a gas-filled syringe is provided which comprises the stepsof forming a container from a gas barrier material to enclose thesyringe, the container comprising a valve, placing the gas-filledsyringe in the container, sealing the container to retain the syringetherein, evacuating the sealed container, and filling the container withthe same gas as in the syringe using the valve.

In accordance with still yet another aspect of the present invention, amethod of preparing a gas-filled syringe is provided which comprises thestep of filling a container with a predetermined volume of a selectedgas via an opening therein. The container is formed from a high gasbarrier material to prevent gas from escaping from the container oncethe opening is sealed. The method further comprises the step ofpuncturing the container with the syringe needle and drawing the gasinto the syringe by retracting the syringe plunger.

A further aspect of the invention is basically attained by providing amethod of introducing a gas into the eye during eye surgery, the methodcomprising the steps of providing a clean and sterile prefilled syringecontaining a unit dose of a pharmaceutically acceptable gas and beingsubstantially free of air and oxygen, the syringe having a syringebarrel, a gas delivery outlet, and a plunger. The syringe is completelyenclosed in a substantially gas impermeable container, and the containerhas an internal volume surrounding the syringe filled with thepharmaceutically acceptable gas at a pressure at least substantiallyequal to atmospheric pressure. The syringe is removed from thecontainer, and the gas delivery outlet is introduced into the eye of apatient and the gas is introduced into the eye.

BRIEF DESCRIPTION OF THE DRAWINGS

These and other features and advantages of the present invention will bemore readily apprehended from the following detailed description whenread in connection with the appended drawings, in which:

FIG. 1 is an isometric view of a container and cover constructed inaccordance with an embodiment of the present invention for containing agas and enclosing a syringe filled with gas;

FIG. 2 is a side cross-sectional view of the container and coverdepicted in FIG. 1 showing the syringe contained therein;

FIG. 3 is a top view of the container depicted in FIG. 1 without thecover or syringe;

FIG. 4 is an isometric view of a container constructed in accordancewith an embodiment of the present invention for containing a gas andenclosing a syringe filled with gas;

FIG. 5 is a side cross-sectional view of the container depicted in FIG.4 showing the syringe contained therein;

FIG. 6 is a side cross-sectional view of a container constructed inaccordance with another embodiment of the present invention forcontaining a gas; and

FIG. 7 is a top view of a syringe and canister in a container in afurther embodiment of the invention.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

With reference to FIG. 1, a container 10 for enclosing a gas syringe 12is shown in accordance with an embodiment of the present invention.Before describing the container 10, an exemplary syringe 12, as shown inFIG. 2, will be described. It is to be understood that other types ofgas-filled syringes can be used in accordance with the presentinvention. The exemplary gas syringe 12 comprises a tubular housing 14defining a syringe barrel having longitudinally cylindrical section 16,a frustoconical section 18 and a gas delivery outlet forming a gasdispensing tip 20 which are all preferably formed as an integral,unitary member. The tubular housing can be formed from a material with ahigh degree of gas impermeability such as glass. The tubular housing,however, can be a gas permeable material such as plastic since thecontainer 10 of the present invention is designed to prevent dilutionand contamination of the syringe contents, as will be described infurther detail below.

With continued reference to FIG. 2, the interior circumference of thetubular housing 14 defines a cavity 22 which can be filled with aselected gas in a conventional manner. The gas is retained within thecavity 22 by a plunger 24. The end of the plunger 24 that is proximalwith respect to the frustoconical section 18 of the housing 14 can beprovided with a stopper 28 which is dimensioned to slidably engage theinner circumference of the cylindrical section 16 of the tubular housing14 to controllably change the level of gas pressurization within thecavity 22. The tip 20 can be fitted with a removable cap 30. Thesyringe, however, can be open at the tip 20, or have a cannula or needleor other delivery device on the tip 20, or have an integral needle ortube molded on the front of the syringe. In any case, the container 10is designed to prevent the gas in the syringe 12 from being diluted orcontaminated by atmospheric air or contaminants regardless of whetherthe cavity 22 is completely sealed.

With reference to FIGS. 1, 2 and 3, the container 10 comprises a bottomportion 32 and a top portion 44. In accordance with an embodiment of thepresent invention, the bottom portion 32 is preferably molded orotherwise formed to create a trough or open container dimensioned to atleast accommodate the syringe 10 having its plunger 24 at leastpartially withdrawn from the cavity 22 of the housing 14. For example,the bottom portion 32 can comprise a bottom wall 38 and four side walls34, 36, 38 and 40 which preferably form a unitary, integral memberdefining a cavity 46 in which the syringe is placed. The tops of theside walls 34, 36, 38 and 40 are each provided with a flange 48, 50, 52and 54. The top portion 44 is dimensioned to cover the opening 56 of thebottom portion 32 of the container 10, as well as engage each flange 48,50, 52 and 54. The top portion 44 and the bottom portion therefore canbe sealed together using, for example, an adhesive 51 on the flanges 48,50, 52 and 54. Alternatively, the material from which the top portion 44and the bottom portion 32 are formed can be fused together via heatsealing, as indicated at 53 in FIG. 5. In either case, the sealed jointformed at the flanges 48, 50, 52 and 54 satisfies the gas barriercriteria sufficient to maintain the purity of the contents (i.e., gas)in the container 10 and syringe 12, if a syringe is placed in thecontainer 10.

Although the bottom portion 32 of the container is shown as rectangularin shape and having a rectangular recess or trough, a variety of shapescan be used. For example, the bottom portion 32 of the container can beformed into a more complicated shape than a rectangle to approximatelyconform to the shape of its contents (e.g., a syringe 12). In addition,the top portion 44 need not be planar. For example, as shown in FIGS. 4and 5, the top portion 44 and the bottom portion 32 of the container 10can both be nonplanar and configured to form the cavity 46 when adheredtogether. Further, the top portion 44 and the bottom portion 32 of thecontainer 10 can be configured to have a curvilinear cross-section (FIG.4) with tapered ends 58 and 60, and 62 and 64, respectively (FIG. 5).The ends are adhered together along the flanges 48, 50, 52 and 54 of thebottom portion and corresponding flanges 66, 68, 70 and 72 of the topportion 44 of the container 10. Alternatively, the top portion 44 andbottom portion 32 of the container 10 can be formed as a unitary andintegral piece of high gas barrier material designated as 74 in FIG. 6which is folded on one side 76 thereof. The two, free ends 78 and 82 arethen sealed with an adhesive layer 83 or by heat sealing depending onthe material used to form the container 10. The container 10 and thesyringe 12 are preferably clean and sterile according to conventionalstandards for surgical equipment.

In accordance with an embodiment of the invention, the container 10 ispreferably made of a high gas barrier material such as a metallizedpolymer laminate which can be sealed to retain a selected gas inside thecontainer. The container 10 is preferably made from a material that issubstantially impermeable to oxygen and other atmospheric gases andsubstantially impermeable to sterilizing gases such as ethylene oxide.The syringe 12 is filled in a conventional manner with a unit dose ofthe selected gas (e.g., sulfur hexafluoride or nitric oxide). Thesyringe 12 is then placed within the bottom portion 32 of the container10 with the plunger 24 at least partially withdrawn from the cavity 22.The container 10 is then filled with preferably the same gas as thesyringe 12 and sealed using the top portion 44 (e.g., by applying anadhesive or heat sealing along the flanges 48, 50, 52 and 54 of thebottom portion 32 to adhere to the edges of the top portion 44).

Alternatively, the container 10 can be made from a sheet 74 of high gasbarrier material that is folded. A gas-filled syringe can be placedbetween the two free ends 78 and 82 of the sheet 74. The space betweenthe free ends is then filled with the same gas and sealed to enclose thegas and gas-filled syringe. Thus, the sealed container 10 provides asufficient gas barrier to prevent the gaseous content of the container,and therefore the syringe, from leaking or diffusing outside thecontainer, and to prevent atmospheric gaseous contaminants fromdiffusing into the container and the syringe. Further, the use of thesame gas inside the container as well as inside the syringe facilitatesthe maintenance of the selected gas within the syringe since any gasexchange occurring through the walls of the syringe does not dilute theunit gas dose therein. The gas within the container is generallymaintained at a pressure to inhibit diffusion of oxygen and otheratmospheric gases into the container, thereby inhibiting dilution of thegas. In embodiments, the gas in the container is at a pressure greaterthan atmospheric pressure.

In preferred embodiments, the gas is a pharmaceutically acceptable gasas known in the medical field which is substantially in the absence ofoxygen, air and other atmospheric gas contaminants. Examples of suitablegases include nitric oxide, nitric oxide releasing compounds, carbondioxide, perfluoropropane, perfluorobutane, perfluoroethane, helium andsulfur hexafluoride. Generally, the gas has a purity level of at least70% by volume and preferably at least about 93% to about 98% by volume.In embodiments, the gas is at least about 97% pure. In preferredembodiments, the syringe and the container are filled with the same gashaving substantially the same purity to inhibit diffusion of gasesbetween the gas in the cavity of the container and cavity of the syringebarrel.

As stated previously, the high gas barrier material for the container 10prevents diffusion of gas molecules from the atmosphere through thecontainer walls and therefore dilution or contamination of the unit gasdose within the syringe 12. The shelf life of the unit gas dose isdetermined by the rate at which gaseous contaminants such as oxygenmolecules from the surrounding atmosphere diffuse into the container 10,or the rate at which the selected gas inside the container 10 diffusesout. The following formula can be used to calculate the maximumallowable gas transmission rate GTR_(MAX) for the container material:${GTR}_{MAX} = {V \times \frac{\left( {1 - P} \right)}{A \times S}}$where V is the volume of the container 10, P is the minimum acceptablepurity of the unit gas dose in the syringe 12, A is the surface area ofthe container 10, and S is the desired shelf life of the unit gas dosein the syringe 12.

By way of an example, a unit dose of sulfur hexafluoride of at leastninety-five percent (i.e., P=95%) purity is desired. The syringe 12 ispackaged in a container 10 having a volume V of 20 cubic inches and asurface area A of 64 square inches. A one year shelf life is desired.The maximum allowable gas transmission rate GTR_(MAX) for the container10 material is therefore 0.0156 cubic inches per square inches per year(or 0.07 cc per 100 square inches per 24 hours). A purity level of 95%in the example above was chosen for illustrative purposes only. Theminimum acceptable purity level of gas can vary, depending on the typeof gas used and the application for its use. Embodiments providinghigher or lower priority levels are covered under the scope of thepresent invention.

Suitable materials for the container 10 can include, but are not limitedto, metal foils such as aluminized foil laminates. Other examples ofcontainer 10 material include laminates having one or more metallizedlayers of nylon, oriented polypropylene (OPP), polyethylene (PE),ethylene vinyl alcohol (EVOH), polyethylene terephthalate (PET), lowdensity polyethylene (LDPE), medium density polyethylene (MDPE), and/orcellophane. A lacquer coating can also be used to create a cold seal.

The container can be made from a suitable gas impermeable laminatehaving a sufficiently low permeability to inhibit or substantiallyprevent the diffusion of air or oxygen from the atmosphere into thecontainer and to inhibit diffusion of the medical gas in the syringe andcontainer from diffusing outward. The container formed from gasimpermeable films are also impermeable to ethylene oxide so that otherforms of sterilization must be used. Gamma radiation at conventionalsterilizing dosages can be used to effectively sterilize the syringe andcontents.

Suitable laminated films include materials sold under the trademarkACLAR by Ted Pella, Inc. which is a transparent fluorinated-chlorinatedthermoplastic. Other materials include silica coated polyester filmssold under the tradename Clearfoil by Rollprint Packaging Products, Inc.of Addison, Illinois, a polypropylene, polyethylene, polyethylene vinylalcohol and Bynel laminate sold under the trademark EVALIGHT by DuPont.Preferably, the container 10 is sufficiently impermeable to oxygen andother atmospheric gases to provide a shelf life of the syringe of aboutone year where the gas purity in the syringe is substantially unchanged.In further embodiments, the packaged syringe has a shelf life of atleast about 6 months to about 5 years, and typically about 1-2 years.

Some of the gases used in surgery have large molecules which cannot passthrough polymeric or metallic films as readily as oxygen. Oxygen andother gaseous contaminants cannot dilute the unit gas dose in thesyringe 12 unless one of two conditions exists. First, if the container10 material allows some of the selected gas in the container to diffuseout into the atmosphere, then the volume of gas lost in the container 10is replaced with other gas constituents from the atmosphere. Second, ifthe pressure in the container 10 is less than atmospheric pressureoutside the container, then the gaseous contaminants may diffuse intothe container regardless of whether any interior container gas diffusesout. If the pressure in the container 10 is essentially maintained abovethe atmospheric pressure, then the container material can be chosen onthe basis of the transmission rate of the gas in the container. In caseswhere the selected gas is characterized by large molecules, materialsproviding considerably lower gas barriers can be used as compared withmaterials providing barriers to gases with relatively small molecules.If the pressure in the container is not maintained above atmosphericpressure, then the highest relevant gas transmission rate, which istypically the gas transmission rate of oxygen in the surroundingatmosphere, is preferably used as the basis for selecting a containermaterial.

A controlled atmosphere of a selected gas inside the container 10 can beachieved in a number of ways. For example, a form/fill/seal machine canbe used. The form/fill/seal machine provides an evacuated assembly areatherein which is filled with the selected gas. The web(s) of a high gasbarrier material selected to construct one or more containers 10 is feedinto the area. One part of the container can be formed, for example,with a recess or trough of sufficient size to accommodate a pre-filledgas syringe therein. The container construction is then completed byenclosing the syringe within the container using, for example, anotherpiece of the web to cover the recess. The other piece of the web can besealed against the first part of the web using an adhesive or heatsealing. The controlled gaseous assembly area, therefore, ensures thatthe container is filled with the same gas as the syringe to avoid theaforementioned problem of dilution caused by gas contaminants mixingwith the contents of the syringe inside the container 10.

Alternatively, a controlled atmosphere of a selected gas inside thecontainer 10 can be achieved by providing the container with a valvewhich permits evacuation of a sealed container having a pre-filled gassyringe enclosed therein and subsequent filling of the container withthe selected gas. Further, the container 10 need not be provided with asyringe 12 at all. In accordance with an embodiment of the presentinvention, the container 10 can be filled with a selected gas (e.g.,using a form/fill/seal machine that does not insert a syringe prior tosealing, or by evacuation, ejection with a selected gas and sealing).The container 10 containing the selected gas can then be drawn into anempty syringe by puncturing the container 10 with a needle and drawingthe gas into the syringe cavity 22 with the plunger 24. Alternatively, asyringe can be constructed with a sufficiently gas impermeable tubularhousing 14, stopper 28 and cap 30 combination to obviate the need for acontainer 10. The syringe can therefore be pre-filled with a selectedgas prior to use and prevent contamination of the gas therein until thecap 30 is removed.

In a further embodiment shown in FIG. 7, a pressurized gas canister 100is coupled to a syringe 102 for filling the syringe 102 with a medicalgas. The canister can be made of metal, plastic, glass or other suitablematerials capable of maintaining the gas under sufficient pressure tofill the syringe. The canister 100 includes a manually operated valve104 having an actuating button 105. The valve 104 has a coupling member106, such as a threaded coupling, for connecting to a filter housing108. The filter housing 108 is typically a HEPA filter as known in theart to remove particulates and other impurities. An outlet coupling 110is provided in the filter housing 108 for connecting to the syringe 102.The syringe 102 in the embodiment illustrated has a luer lock typefitting for coupling to the filter. In further embodiments, the syringecan have a needle for piercing a septum or membrane on the outletcoupling 110 of the filter housing 108. Alternatively, the syringe canhave a tapered tip for attaching to the coupling 110 and for receiving aneedle or other delivery outlet or device. In use, the button 105 isdepressed to release the gas from the canister to fill the syringe.Typically, the canister containers a sufficient amount of gas to flushthe syringe to remove any contaminants which may be present. Inembodiments of the invention, the syringe and canister are enclosed in acontainer 112 having a cavity 114 containing the same gas as the gas inthe canister. Preferably, the gas in the canister and the container 112is substantially pure in the absence of oxygen and other atmosphericgases. The container 112 is made from the same materials as in theprevious embodiments.

The container 10, whether it is provided with a syringe 12 therein ornot, is preferably sterilized so it can be used in surgery, for example.A number of methods for sterilization can be used. The container 10 canbe sterilized, for example, as it is being formed inside aform/fill/seal machine. The syringe can be sterilized before it isinserted into a sterile chamber in the form/fill/seal machine, or thesyringe 12 and new formed container 10 can both be sterilized as theyare assembled together. A container 10 containing only gas and nosyringe can be sterilized inside a form/fill/seal machine or besterilized after it is assembled and before it is filled with gas if anatmosphere-controlled assembly and fill area is not available.

In accordance with the present invention, a pre-filled packagecontaining a unit dose of medical gas and method of making same isprovided. The pre-filled package can be a package, a package containinga syringe or a syringe having a gas impermeable chamber. The pre-filledpackage prevents contamination of the gas therein for use in a number ofapplications, such as injection of a gas bubble into a patient's eye fortreating a retinal tear, or injection of carbon dioxide into a bloodvessel to displace blood and allow an improved field of view duringpercutaneous angioscopy. The material with which the package is made isselected to maintain a desired purity level of gas within the package.Further, the aforementioned problems associated with dispensingexpensive gases from a tank in preparation for a medical procedure areavoided.

In the method of the invention, the syringe is removed from thecontainer and the delivery device, such as a needle, is introduced inthe desired location in the body of the patient being treated. Thesyringe plunger is then depressed to inject a unit dose of the gas intothe patient. The gas can be injected into a vein or vessel, the ocularcavity of an eye during eye surgery, the spinal column, and the like, asknown in the medical and surgical field. When performing surgery in theeye, such as retinal surgery, the injected gas is an ophthalmologicallyacceptable gas.

While certain advantageous embodiments have been chosen to illuminatethe invention, it will be understood by those skilled in the art thatvarious changes and modifications can be made herein without departingfrom the scope of the invention as defined in the appended claims.

1. A gas syringe unit for injecting a gas into the body of an animal,said syringe unit comprising: a prefilled gas syringe containing a unitdose of a pharmaceutically acceptable gas, said gas being substantiallyin the absence of air, said syringe including a syringe barrel with agas delivery outlet, and a plunger slidably received in said syringebarrel for expelling said unit dose of said gas through said deliveryoutlet; and a container having an internal volume and being configuredand arranged to enclose said gas syringe within the internal volume andso to prevent contact of said gas syringe with air and contaminantsexternal to said container, the internal volume containing saidpharmaceutically acceptable gas substantially in the absence of air,wherein said container is made of a material characterized as having agas transmission rate sufficient to essentially prevent saidpharmaceutically acceptable gas from diffusing out of the containerinternal volume and to essentially prevent atmospheric contaminants fromdiffusing into the container interior volume, and said container havingan internal pressure to inhibit diffusion of air and contaminants intosaid container.
 2. The gas syringe of claim 1, wherein said containerhas an internal surface area defining said unit dose of said gas, andsaid gas in said syringe has a purity of at least about 95%, said gashaving a shelf life of at least one year, said container material havinga maximum allowable gas transmission rate determined using V×(1−p)/(A×S), wherein V is a volume of said container, p is the purity ofsaid gas, A is the internal surface area of said container, and S issaid shelf life.
 3. The gas syringe of claim 1, wherein said gas isselected from the group consisting of nitric oxide, nitricoxide-releasing compounds, carbon dioxide, perfluoropropane,perfluorobutane, perfluoroethane, helium, and sulfur hexafluoride. 4.The gas syringe of claim 1, wherein said container material is selectedfrom the group consisting of a metal foil, an aluminized foil laminate,and a laminate having at least one metallized layer of at least onelayer of nylon, polypropylene, ethylene vinyl alcohol, polyethyleneterephthalate, low density polyethylene, medium density polyethylene orcellophane.
 5. The syringe of claim 1, wherein said gas delivery outletis a needle.
 6. The syringe of claim 1, wherein said gas issubstantially free of oxygen and is at least about 93% by volume pure.7. The syringe of claim 1, wherein said gas in said container is at apressure above atmospheric pressure.
 8. The syringe of claim 1, whereinsaid container is made from a metal foil laminate.
 9. The syringe ofclaim 1, further comprising a canister containing said pressurized gas,said canister having an outlet removably coupled to said delivery outletfor supplying said gas to said syringe.
 10. A method of forming a gasbubble in the body of a patient, said comprising the steps of: providinga clean and sterile packaged, prefilled syringe having a syringe barrel,delivery outlet and plunger, said syringe containing a unit dose of apharmaceutically acceptable gas, said gas being substantially free ofair, wherein said prefilled syringe is enclosed in a container, saidcontainer being formed from a material characterized as having a gastransmission rate sufficient to essentially prevent said gas fromdiffusing out of the container and to essentially prevent atmosphericcontaminants from diffusing into the container interior volume andhaving an internal volume surrounding said syringe and being filled withsaid gas at a pressure at least substantially equal to atmosphericpressure, removing said syringe from said container, introducing saidsyringe delivery outlet into the patient, and injecting saidpharmaceutically acceptable gas via the syringe delivery outlet into thepatient, thereby forming a gas bubble of the pharmaceutically acceptablegas within the patient.
 11. The method of claim 10, wherein saiddelivery outlet is a needle or cannula.
 12. The method of claim 10,wherein said pharmaceutically acceptable gas has a purity of at leastabout 70% by volume.
 13. The method of claim 10, wherein saidpharmaceutically acceptable gas has a purity of about 93% to 98% byvolume.
 14. The method of claim 10, wherein said container has a gaspermeability to provide a shelf life of said gas in said syringe of atleast one year.
 15. The method of claim 10, wherein saidpharmaceutically acceptable gas is selected from the group consisting ofnitric oxide, nitric oxide-releasing compounds, carbon dioxide,perfluoropropane, perfluoroethane, perfluorobutane, helium and sulfurhexafluoride.
 16. The method of claim 10, wherein said containermaterial is made from a laminate material having at least one metal foillayer and a layer selected from the group consisting of nylon,polypropylene, polyethylene, ethylene vinyl alcohol, polyethyleneterephthalate and cellophane.
 17. The method of claim 10, wherein saidcontainer material has a sufficiently low gas permeability whereby thepurity of said pharmaceutically acceptable gas in said container issubstantially unchanged after about one year.
 18. The method of claim10, wherein said container material is substantially oxygen impermeablematerial.
 19. The method of claim 10, wherein said pharmaceuticallyacceptable gas in said container is at a pressure above atmospheric. 20.A method of forming a gas bubble in an eye of a patient during eyesurgery, said method comprising the steps of providing a clean andsterile prefilled syringe containing a unit dose of a pharmaceuticallyacceptable gas and being substantially free of air and oxygen, saidsyringe having a syringe barrel, a gas delivery outlet, and a plunger,said syringe being completely enclosed in a container of a materialcharacterized as having a gas transmission rate sufficient toessentially prevent said gas from diffusing out of the container and toessentially prevent atmospheric contaminants from diffusing into thecontainer interior volume, said container having an internal volumesurrounding said syringe and being filled with said pharmaceuticallyacceptable gas at a pressure at least substantially equal to atmosphericpressure, removing said syringe from said container, introducing saidgas delivery outlet of said syringe into the eye of the patient andintroducing said pharmaceutically acceptable gas into the eye so as toform the gas bubble within the eye, and wherein said pharmaceuticallyacceptable gas is selected from the group consisting of nitric oxide,nitric oxide-releasing compounds, carbon dioxide, perfluoropropane,perfluoroethane, perfluorobutane, helium and sulfur hexafluoride. 21.The method of claim 20, wherein said pharmaceutically acceptable gas hasa purity of at least about 93% to 98% by volume.
 22. A method forpreparing a gas syringe unit, comprising the steps of: forming acontainer from a substantially gas impermeable material, the containerhaving an internal volume; providing a prefilled gas syringe containinga unit dose of a pharmaceutically acceptable gas, said gas beingsubstantially in the absence of air, said syringe including a syringebarrel with a gas delivery outlet, and a plunger slidably received insaid syringe barrel for expelling said unit dose of said gas throughsaid delivery outlet; disposing the prefilled gas syringe within thecontainer internal volume; filling the container internal volume withthe pharmaceutically acceptable gas so the gas within the internalvolume is at a pressure at least substantially equal to atmosphericpressure.
 23. The method of claim 22, wherein said disposing includessealing the container so as to retain the prefilled gas syringe withinthe container; and whrrein said method further comprises the step of:evacuating the sealed container and thereafter filling the containerinternal volume with the pharmaceutically acceptable gas.
 24. The methodof claim 23, wherein the container is configured and arranged so as toinclude a valve and wherein said evacuating and said filling isaccomplished using the valve.